PHAR3820 Drugs

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1

Paracetamol

Simple analgesic - equal first line treatment of tension headache and acute migraine (non-opioid analgesics)

Dose: Soluble 1g orally; Max 4g in 24 hours.

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Aspirin

NSAID - equal first line treatment of tension headache and acute migraine (non-opioid analgesics)

Dose: 600-900mg, Max 2g in 24 hours.

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Ibuprofen

NSAID - equal first line treatment of tension headache and acute migraine (non-opioid analgesics)

Dose: 400mg, Max 2.4g in 24 hours.

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Diclofenac

NSAID - equal first line treatment of tension headache (non-opioid analgesics)

Dose: 50mg, Max 150mg in 24 hours.

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5

Amitriptyline (headache)

TCA - First line prophylaxis of tension headache

Dose: 10mg at night

Increase dose by 10mg every 7 days, max 75mg at night, for 8 weeks.

If effective, continue for 6 months.

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Nortryptiline (headache)

TCA - First line prophylaxis of tension headache

Dose: 10mg at night

Increase dose by 10mg every 7 days, max 75mg at night, for 8 weeks.

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Mirtazapine (headache)

Tetracyclic antidepressant - Second line prophylaxis of tension headache. Used if first line ineffective after 8-12 weeks. Patient should be referred to a specialist.

Dose: 15-30mg at night for 8-12 weeks

If ineffective, refer to specialist.

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Venlafaxine (headache)

SNRI - Second line prophylaxis of tension headache. Used if first line ineffective after 8-12 weeks. Patient should be referred to a specialist.

Dose: 75mg in the morning after food, up to 150mg daily, for 8-12 weeks.

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Metoclopramide

Dopamine antagonist Antiemetic - Second line treatment in migraine is nausea present. Also helps increase absorption of simple analgesic due to decreased gut motility.

Not recommended for use in Parkinson's Disease - can worsen symptoms. Dose: 10mg orally, max 30mg.

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10

Domperidone

Dopamine antagonist Antiemetic - Second line treatment in migraine if nausea present. Also helps increase absorption of simple analgesic due to decreased gut motility.

Dose: 10-20mg orally, max 30mg.

Not recommended for use in Parkinson's Disease - can worsen symptoms.

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11

Ondansetron

5HT3 antagonist Antiemetic - Second line treatment in migraine if nausea present. Also helps increase absorption of simple analgesic due to decreased gut motility.

Dose: 4-8 mg orally, max 16mg.

Do not use in patients on MAO inhibitors!!

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12

Eletriptan

5-HT1B/D/F agonist (Triptan) - 3rd line treatment of migraine headache

Dose: 40-80mg orally. If symptoms recur, wait at least 2 hours before repeating the dose. Max 160mg.

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Sumatriptan

5-HT1B/D/F agonist (Triptan) - 3rd line treatment of migraine headache

Dose: 20mg intranasally. If symptoms recur, wait at least 2 hours before repeating the dose. Max 40mg.

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Naratriptan

5-HT1B/D/F agonist (Triptan) - 3rd line treatment of migraine headache

Dose: 2.5mg orally. If symptoms recur, wait at least 4 hours before repeating the dose. Max 5mg.

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15

Lasmiditan

Selective serotonin 5-HT1F receptor agonist - novel treatment of migraine headache

The lack of affinity for 5-HT1B and 5-HT1D may (not conclusive) result in fewer side effects related to vasoconstriction compared to triptans

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16

Erenumab

Recombinant human monoclonal antibody that competitively inhibits CGRP receptor. Used for prophylaxis in migraine.

Dose: SC injection 70 or 140mg monthly.

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17

Olcegepant

Non-peptide CGRP antagonist. Though to be effective in preventing migraine by inhibiting neurogenic vasodilation and neuronal excitability, but clinical studies failed due to liver toxicity concerns and was not orally active.

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18

Ubrogepant

Orally available small molecule antagonist of CGRP receptor. Still in development.

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19

Rimegepant

Orally available small molecule antagonist of CGRP receptor. Still in development. Undergoing phase III clinical trials in Australia.

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20

Buspirone

5HT-1A partial agonist. Used as an anxiolytic agent (not available in Australia)

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21

Vortioxetine

Atypical antidepressant - multimodal 5-HT actions (both agonist and antagonist) and SERT inhibition. Used in major depression.

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22

Ketamine/Esketamine

Blocks the NMDA receptor and stimulates the AMPA glutamate receptor, causing an increase in brain neurotrophic signalling that restore synaptic function in certain brain regions.

Injectable, very potent, rapidly acting anaesthetic Does not relax skeletal muscles, so can only be used alone in procedures of short duration (ketamine).

Used off-label to treat treatment-resistant depression (esketamine).

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23

Allopregnanolone (Brexanolone)

Neuroactive steroid - positive allosteric modulator of GABA-A receptors. Emerging evidence for use in postpartum depression, not yet available in Australia.

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24

Gingko biloba

Complimentary medicine used in dementia. Potentially some benefit in managing symptoms, but not prevention.

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25

Omega 3 Fatty Acids

Complimentary medicine used in dementia. No evidence for efficacy in prevention or symptom management.

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26

Vitamin E

Complimentary medicine used in dementia. Some evidence that may slow functional decline in AD.

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27

Benzodiazepines (status epilepticus)

Used for immediate intervention in status epilepticus (5 min continuous or repetitive seizures). Intranasal or buccal forms preferred to avoid the patient having to swallow anything. IV also can be used.

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28

Carbamazepine

Antiepileptic - Antagonist of voltage-dependent and use-dependent sodium channels. First line prevention of partial seizures.

Autoinduces own metabolism – as more is used, metabolism becomes more efficient, more has to be used. Increase dose slowly.

May also be used as a mood stabiliser in behavioural and psychological symptoms of dementia (BPSD), bipolar disorder for maintenance (third line), and treatment of acute depressio (weak evidence) and mania (not first line).

Do NOT use in pregnancy.

ADR: Diplopia (double vision) earliest sign of toxicity, 10% morbilliform rash (looks like measles)

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29

Sodium Valproate

Antiepileptic - Multiple mechanisms. Inhibits voltage‑ and use-dependent sodium channels, enhances GABA, inhibits glutamate and T-type calcium channels. First line prevention of generalised seizures.

Also used as a mood stabiliser in combination with antipsychotic therapy for maintenance of bipolar, and acute treatment of mania, and for behavioural and psychological symptoms of dementia (BPSD)

ADR: TERATOGENICITY (dosing is gender specific), sedation, hair loss, weight gain are common

Do NOT use in pregnancy.

Unpredictable Drug-drug interactions

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30

Lamotrigine

Antiepileptic - Antagonist of voltage-dependent and use-dependent sodium channels. Second line for both partial and general epilepsy. Non-inferior to carbamazepine

Also indicated for treatment of acute bipolar depression, and third line maintenance treatment of bipolar (in combination with an antipsychotic)

Do NOT use in pregnancy.

ADR: Stevens-Johnson Syndrome (especially if used with sodium valproate).

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31

Oxcarbazepine

Antiepileptic - Antagonist of voltage-dependent and use-dependent sodium channels. Second line for partial and generalised tonic-clonic seizures.

Structurally related to carbamazepine but does not autoinduce metabolism and less interactions.

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32

Ethosuxamide

Antiepileptic - Inhibits T-type calcium channel conductance in thalamic neurones. First choice monotherapy for absence seizure prophylaxis.

Does not prevent tonic-clonic activity (do not use in mixed seizures)

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33

Levetiracetam

Antiepileptic - Exact mechanism unknown. May modulate neurotransmission by binding to synaptic vesicle protein 2A (SV2). First line for Tonic-clonic seizures where generalised or partial onset is unclear in Females

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34

Topiramate

Antiepileptic - Antagonist of voltage-dependent and use-dependent sodium channels. Third line, used as adjunct treatment for partial and generalised seizures.

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35

Phenytoin

Antiepileptic - Antagonist of voltage-dependent and use-dependent sodium channels. Adjunct treatment for partial seizures.

Low therapeutic index (narrow safety margin) - TDM required.

ADR: CNS toxicity including nystagmus and ataxia (concentration dependent)

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36

Lacosamide

Antiepileptic - Exact mechanism unknown, may promote slow activation of voltage-dependent sodium channels. Adjunct treatment for partial seizures.

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37

Tiagabine

Antiepileptic - Inhibits neuronal GABA reuptake by inhibiting GAT1, increasing GABA-mediated inhibition. Adjunct treatment for partial seizures.

May also be used to improve sleep in older people/cocaine users

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38

Zonisamide

Antiepileptic - Exact mechanism unknown, may blockvoltage-dependent sodium and T‑type calcium channels, and modulate GABA-mediated neuronal inhibition. Adjunct treatment for partial seizures.

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39

Phenobarbital

Barbiturate antiepileptic - Positive allosteric modulator of GABA receptors. Adjunct treatment for partial seizures.

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40

Midazolam

Benzodiazpine antiepileptic- Positive allosteric modulator of GABA receptors (over a longer term than barbiturates). Adjunct treatment for partial seizures. Short acting benzodiazepine (half life <5 hours)

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41

Ganaxolone

A synthetic neuroactive steroid related to allopregnanolone. It has sedative, anxiolytic, and anticonvulsant effects. It is undergoing Phase 2 clinical trials for drug-resistant partial onset seizures. Quite different SE profile to benzos and barbiturates.

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42

Perampanel

Antiepileptic - Selective non-competitive antagonist of AMPA (glutamate) receptors. Effective in the treatment of refractory partial-onset seizures.

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43

Vigabatrin

Antiepileptic - Irreversibly inhibits GABA aminotransferase, increasing GABA-mediated inhibition. Used only for refractory (uncontrolled) epilepsy.

ADR: Visual field defects (20-40% of patients)

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44

Gaboxadol/THIP

GABA-A Agonist - reached phase III trials for insomnia treatment. Entering trials for Fragile X syndrome.

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45

Bicuculline

GABA-A competitive antagonist. Causes convulsions.

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46

Baclofen

GABA-B receptor agonist - used as a muscle relaxant.

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47

γ-Hydroxybutyric Acid (GHB)

GABA-B Agonist, and at a subset of GABA-A receptors. Used for treating narcolepsy, alcoholism, also a street drug (fantasy)

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48

Alprazolam

Short acting benzodiazepine - half life 10 hours. Used for short term treatment of insomnia and acute anxiety states.

Dose: 10-30mg 30 mins before bed

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49

Oxazepam

Short acting benzodiazepine - half life 4-15 hours. Used for short term treatment of insomnia and acute anxiety states. Safe to use in liver failure.

Dose: 7.5-30mg at night.

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50

Nitrazepam

Medium-long acting benzodiazepine - half life 16-48 hours. Used for short term treatment of insomnia.

Dose: 5-10mg just before bed.

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51

Flunitrazepam

Long acting benzodiazepine - half life 20-30 hours. Used for short term treatment of insomnia.

Dose: 1-2mg at night

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52

Zolpidem

Positive allosteric modulator of GABA-A receptors - Specific binding to receptors containing α1 subunit (but there is still a potent effect when bound to α2,α3 receptors)

Binds with higher affinity to the α1 containing receptors, and has no appreciable affinity at for α5 containing receptors - sedative efefcts without short-term memory loss Dose: 10mg just before bed

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53

Zopiclone

Positive allosteric modulator of GABA-A receptors - Specific binding to receptors containing α1 subunit (but there is still a potent effect when bound to α2,α3 receptors)

Has anxiolytic actions due to higher efficacy at α3-containing receptors Dose: 7.5mg just before bed

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54

Ritanserin

5-HT2A and 5-HT2C receptor antagonist, promotes non-REM sleep but safety concerns have curbed trials.

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55

Eplivanserin

Inverse agonist on the 5-HT2A receptor. Withdrawn from FDA application on basis of lack of efficacy for insomnia.

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56

Amitriptyline

TCA - inhibits reuptake of NA and 5-HT. Also blocks cholinergic, histaminergic, alpha1 -adrenergic and serotonergic (5HT1a, 1b, 2a, b, c and 3) subtypes receptors.

Indicated for major depression. Also used off-label for sedation.

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57

Mirtazapine

Tetracyclic antidepressant - postsynaptic blockade of serotonin 5HT2 and 5HT3 receptors and presynaptic blockade of central alpha2-adrenergic inhibitory autoreceptors. It is also a potent H1 antagonist which accounts for its sedative effects.

Indicated for major depression. Also used off-label for sedation.

Widely used in conjunction with venlafaxine (or an SSRI) in treatment-resistant depression.

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58

Agomelatine

Antidepressant - Mechanism not fully understood, MT1 and MT2 agonist and 5HT2C receptor antagonist. Has chronotropic activity.

Indicated for major depression (last line). Also used off-label for sedation.

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59

Quetiapine

2nd Generation (atypical) Antipsychotic - 5HT2A/D1-2 (main effect) H1 and NAα1antagonist and partial 5HT1A agonist

Indicated for schizophrenia, bipolar disorder (including depressive episodes), adjunct in treatment-resistant major depression, and generalized anxiety disorder. Also used off-label for sedation.

Safest antipsychotic option (aside from clozapine) for dementia in Parkinson's disease.

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60

Suvorexant

Dual orexin receptor 1 & 2 antagonist (DORA) - block the binding of wake-promoting orexin A and B neuropeptides. Approved for insomnia in 2016 by TGA.

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61

Ramelteon

MT1/MT2 receptor agonist. Quite effective in insomnia, but not marketed in Australia. Provides fast changes in SOL.

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62

Melatonin

Chronobiotic - Acts on MT1 and MT2 receptors. Resets body clock rather than sedative. Used for insomnia in adults/older people.

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63

Triazolam

Short acting benzodiazepine (half life <5 hours)

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64

Temazepam

Intermediate acting benzodiazepine (half life 5-24 hours). Used for short term treatment of insomnia and acute anxiety states. Safe to use in liver failure.

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65

Lorazepam

Intermediate acting benzodiazepine (half life 5-24 hours). Safe to use in liver failure.

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66

Clonazepam

Intermediate acting benzodiazepine (half life 5-24 hours)

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67

Clorazepate

Long acting benzodiazepine (half life >24 hours)

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68

Clordiazepoxide

Long acting benzodiazepine (half life >24 hours)

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69

Diazepam

Long acting benzodiazepine (half life >24 hours). Used for short term treatment acute anxiety states and acute alcohol withdrawal.

Can also be used as treatment of Serotonin Syndrome and Anticholinergic syndrome

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70

Flurazepam

Long acting benzodiazepine (half life >24 hours)

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71

Lithium

Mood stabilising agent, first line (gold standard) for maintenance of bipolar disorder, but can also be used for treatment of manic and depressive states in bipolar.

Added to antidepressant therapy in treatment-resistant depression.

Low therapeutic index (narrow safety margin) - requires TDM

Avoid use in pregnancy, especially 1st trimester. (However, continuing lithium may be the best option as poorly controlled bipolar disorder may compromise maternal health and carbamazepine, valproate and lamotrigine are not suitable alternatives during pregnancy)

ADR: diabetes insipidus, hypothyroidism

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72

Aripiprazole

2nd Generation (Atypical) Antipsychotic. Indicated for maintenance of psychotic disorders (e.g. schizophrenia) and bipolar disorder, and may be used in combination with a mood stabiliser for acute mania in bipolar disorder.

Added to antidepressant therapy in treatment-resistant depression.

Lower risk of ADRs compared to other antipsychotics.

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73

Haloperidol

1st Gen (Typical) Antipsychotic. Indicated for maintenance of psychotic disorders (e.g. schizophrenia) and bipolar disorder, and may be used in combination with a mood stabiliser for acute mania in bipolar disorder.

High risk of increased prolactin levels and EPSE,

More likely than other antipsychotics to cause QT prolongation (likely dose related)

Comes in LAI form

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74

Olanzapine

2nd Generation (Atypical) Antipsychotic. Indicated for maintenance of psychotic disorders (e.g. schizophrenia) and bipolar disorder, acute bipolar depression, and may be used in combination with a mood stabiliser for acute mania in bipolar disorder.

Used in conjunction with fluoxetine in treatment resistant depression.

May reduce anxiety around weight and shape, compulsive hyperactivity, delusions and mood lability in eating disorders.

Not used for first episode psychosis due to side effect profile (weight gain, metabolic side effects e.g. increased risk of diabetes, dyslipidemia)

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75

Chlorpromazine

1st Gen (Typical) Antipsychotic. Indicated for maintenance of psychotic disorders (e.g. schizophrenia) and bipolar disorder, and may be used in combination with a mood stabiliser for acute mania in bipolar disorder.

Can also be used as an antidote for severe Serotonin Syndrome

Wide range of side effects, including sedation, anticholinergic effects, hypotension and metabolic effects.

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76

Clozapine

2nd Gen (Atypical) Antipsychotic. Very effective, but only used for treatment refractory schizophrenia (trial of 2 other APs first) due to haematological and cardiovascular side effect profile.

Low risk of EPSE and hyperprolactinaemia, but high side effect risk for all other antipsychotic side effects e.g. sedation, weight gain, hyperglycaemia, anticholinergic effects, hypotension , dyslipidemia

Off label uses: Bipolar disorder, psychosis associated with Parkinson’s disease

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77

Lurasidone

2nd Gen (Atypical) Antipsychotic. Indicated for maintenance of psychotic disorders (e.g. schizophrenia), and as both monotherapy and adjunct therapy in acute bipolar depression. Third line for maintenance in bipolar disorder in combination with a mood stabiliser.

High risk of weight gain and metabolic side effects

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78

Risperidone

2nd Generation (Atypical) Antipsychotic. Indicated for maintenance of psychotic disorders (e.g. schizophrenia) and bipolar disorder, and may be used in combination with a mood stabiliser for acute mania in bipolar disorder.

Only antipsychotic PBS listed for treatment of behavioural and psychological symptoms of dementia (BPSD) - second line to non-pharm interventions

Risk for metabolic side effects like other second gen antipsychotics, but also has high risk of hyperprolactinaemia which is uncharacteristic of the second gen antipsychotics.

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79

Escitalopram

SSRI Antidepressant - Indicated for major depression and anxiety disorders.

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80

Venlafaxine

SNRI Antidepressant - indicated for major depression, may have some benefit in anxiety disorders. Generally less well tolerated than SSRIs.

Widely used in conjunction with mirtazapine in treatment-resistant depression.

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81

Fluoxetine

SSRI Antidepressant - Indicated for major depression and anxiety disorders.

Used in combination with olanzapine in treatment-resistant depression.

Strong evidence that may reduce binge eating and purging in high doses for bulimia nervosa.

Has a longer half life than other SSRIs (decreased risk of withdrawal effects), but requires a longer washout period.

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82

Nortriptyline

TCA - indicated for major depression, second line.

Less hypotension and anticholinergic ADRs in the elderly

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83

Reboxetine

NRI antidepressant, also has weak SRI activity - indicated for major depression.

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84

Phenelzine

MAOI Antidepressant - third line for major depression, and anxiety disorders.

Risk of hypertensive crisis when foods containing tyramine are eaten while on this medication.

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85

Bupropion

Atypical antidepressant, unknown mechanism of action - indicated for treatment of nicotine dependence. Used as an adjunct to SSRI in treatment-resistant depression.

Action may be due to inhibition of neuronal reuptake of dopamine and noradrenaline. Also a non-competitive antagonist at α3β2, α3β4 and α4β2 nACh receptors

Less effective than varenicline and combination NRT in smoking cessation

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86

Psilocybin

Novel treatment of depression, PTSD, alcohol and tobacco dependence combined with psychological counselling.

May reduces rigid patterns of rumination and anxiety.

Currently schedule 9 - contained in magic mushrooms.

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87

Modafinil/armodafinil

Non-amphetamine psychostimulant - First line in international guidelines for narcolepsy (but not on PBS).

MOA: Weak competitive binding to cell membrane DATs in the vPAG area and NETs in the VLPO area. Downstream effects are enhanced histamine and orexin release which stabilises wakefulness.

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88

Dexamphetamine (narcolepsy)

Psychostimulant - first line treatment of narcolepsy in Australia. Promote release of catecholamines and block NA and DA reuptake.

Dose = 10 mg mane initially then increase up to 60 mg d in divided doses

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89

Methylphenidate (narcolepsy)

Psychostimulant - first line treatment of narcolepsy in Australia. Blocks NA and DA reuptake.

Dose = Initially 5 mg twice daily (morning and noon); gradually increase to 20–30 mg daily given in divided doses to a maximum of 60 mg daily.

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90

Sodium Oxybate

Used in narcolepsy outside of Australia (currently unregistered in Aus). Acts as a partial weak agonist at GABA receptors and involved in the release of neurotransmitters.

Has initial drowsy effects, but wakefulness effects once initial dose wears off (1 dose taken at night time before bed and another dose taken during the night)

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91

Solriamfetol

Inhibits DA/NE reuptake through DAT/NET. Used in narcolepsy outside of Australia.

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92

Pitolisant

H3R antagonist/inverse agonist – has wake promoting and anticataplectic effects by blocking inhibitory effect of histamine on histamine release. Used in narcolepsy outside of Australia.

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93

Caffeine

Binds to adenosine receptors a1 and blocks adenosine actions to cause wakefulness. Alertness effects now considered to be withdrawal reversal.

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94

Clomipramine

TCA - indicated for major depression, OCD, and cataplexy in narcolepsy.

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95

Pregabalin

Gabapentinoid - indicated for neuropathic pain and as an adjunct treatment for partial seizures.

Binds to alpha-2 delta protein subunit of high threshold voltage-dependent calcium channels, reducing calcium influx and neurotransmitter release.

High potential for misuse - euphoria a common side effect. Non-saturable absorption, quickly absorbed, high levels of binding at site of action (6x higher than gabapentin).

Many off label uses - "opioid sparing", sedation, GAD, alcohol use disorder, restless legs syndrome, PTSD, inflammatory arthritis, postoperative pain, benzodiazepine withdrawal management

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96

Gabapentin

Gabapentinoid - indicated for neuropathic pain and as an adjunct treatment for partial seizures.

Binds to alpha-2 delta protein subunit of high threshold voltage-dependent calcium channels, reducing calcium influx and neurotransmitter release.

Lower potential for misuse - has saturable metabolism, absorbed more slowly, lower binding at site of action.

Many off label uses - "opioid sparing", sedation, alcohol use disorder, restless legs syndrome, PTSD, inflammatory arthritis, postoperative pain, benzodiazepine withdrawal management

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97

Donezepil

Cholinesterase inhibitor - decreases breakdown of acetylcholine. Modest efficacy in improving cognition and/or reducing the rate of cognitive and functional decline in alzheimer's disease.

Similar efficacy to other ChEIs. Well tolerated, possibly due to lack of BuChE effects

Lowered β-amyloid in vitro - potential additional effect, but unfortunately does not in vivo

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98

Rivastigmine

Cholinesterase inhibitor - decreases breakdown of acetylcholine. Modest efficacy in improving cognition and/or reducing the rate of cognitive and functional decline in alzheimer's disease.

Similar efficacy to other ChEIs, but at higher doses thought to have more GI side effects.

Shows some selectivity in areas of the brain more affected by neuronal degeneration - inhibits AChE more potently in cortex and hippocampus, and more effective against monomeric form of the enzyme which is present in relatively higher conc in these areas of AD patients

Inhibits both AChE and Butyrylcholinesterase.

Gaining popularity as an antidote to Anticholinergic toxicity

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99

Galantamine

Cholinesterase inhibitor - decreases breakdown of acetylcholine. Modest efficacy in improving cognition and/or reducing the rate of cognitive and functional decline in alzheimer's disease.

Also used to reverse the muscular effects of gallamine triethiodide and tubocurarine (neuromuscular blockers used in surgery)

Similar efficacy to other ChEIs. Well tolerated, possibly due to lack of BuChE effects

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100

Memantine

N-methyl-D-aspartate (NMDA) antagonist - may block glutamate excitotoxicity or improve function of hippocampal neurons in Alzheimer's Disease. Indicated in moderate to severe AD.

Uncompetitive open channel blocker - higher degree of channel blockade in presence of excessive glutamate, i.e. when the receptor is being overly activated – neuroprotective effect

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